随着生活水平的提高，高脂血症性骨质疏松的病人越来越多，但是单纯的骨合成代谢疗法并不能完全治疗合并高脂血症的骨质疏松症。结合文献和我们前期的研究结果证实：高脂血症时体内升高的ROS和ox-lipids所引起的氧化应激损伤会导致BMSCs细胞衰老，从而引发骨质疏松症。LRP6是正向调控骨形成的关键因子，临床研究发现LRP6基因缺陷的人群会出现早衰，同时合并严重的高脂血症和骨质疏松症。我们前期研究还发现LRP6是ox-lipids的受体，能参与体内ox-LDL的摄取清除，降低ROS水平。因此，本项目拟通过整体动物和细胞实验证实：高脂血症时LRP6参与骨髓微环境内ox-lipids的清除调节，通过降低ROS水平，保护BMSCs不受氧化应激的刺激，防止BMSCs发生细胞衰老，维持BMSCs的成骨分化能力，避免骨质疏松的发生发展。希望通过阐明这一机制能为研发新型抗骨质疏松靶向治疗药物提供理论基础。

With the developing of economy, there are more and more patients suffer from hyperlipidemia-induced osteoporosis, while only using osteosynthesis promoting therapy can not treat these patients completely. Combined with the literature and our previous data, it is confirmed that the oxidative stress damage caused by ROS and ox-lipids in hyperlipidemia will promote cellular senescence of BMSCs cells and lead to osteoporosis finally. LRP6 is a key factor to regulate bone formation. Clinical studies show that people with LRP6 gene defects will suffer from premature aging, severe hyperlipidemia and osteoporosis. Our previous study also found that LRP6 is the receptor of ox-lipids, which can participate in the uptake and clearance of ox-LDL in vivo and reduce the level of ROS. Therefore, this project intends to confirm through the overall animal and cell experiments that LRP6 is involved in the clearance of ox-lipids in the bone marrow microenvironment during hyperlipidemia, by reducing the level of ROS, protecting BMSCs from the stimulation of oxidative stress, preventing BMSCs from cellular senescence, maintaining the osteogenic ability of BMSCs, and avoiding the occurrence and development of osteoporosis. It is hoped that this mechanism can provide a theoretical basis for the development of new targeted anti-osteoporosis drugs.